Multiple myeloma: reduced plasma cell contamination in peripheral blood progenitor cell collections performed after repeated high‐dose chemotherapy courses

Abstract

Summary. The possibility of reducing tumour cell contamination by cytotoxic drug courses prior to peripheral blood progenitor cell (PBPC) collection was evaluated in two consecutives groups of multiple myeloma (MM) patient candidates for autograft. All patients were at disease onset and received two VAD (vincristine, doxorubicin and dexamethasone) courses as initial debulking. In the first group (44 patients), mobilization and harvest were performed 'upfront', after a single cyclophosphamide (CY) administration of 4 g/m 2 ; in the second group (17 patients), PBPC were collected at the end of a high-dose sequential chemotherapy programme, including: CY 5 g/m 2 , etoposide (VP16) 2 g/m 2 , a chemotherapy-free interval with three courses of high-dose dexamethasone, a final mobilizing CY at 7 g/m 2 . G-CSF was given following each high-dose cytotoxic drug. Cytofluorimetric analysis was performed to quantify progenitors (CD34 þ cells) and plasma cells, identified by the high CD38 expression and/or CD38 and CD138 coexpression.Large amounts of PBPC were collected in either group (median harvested CD34 þ

CD34+ selection of autologous peripheral blood stem cells for transplantation following sequential cycles of high-dose therapy and mobilisation in multiple myeloma

“…This value is in close agreement with reported levels. 13,40 The extent of depletion of CD38 ++ cells as a result of CD34 + selection correlated with the burden of these cells in the leukapheresis product. As a result of CD34 + selection there were 500-fold less CD38 ++ cells in the CD34 + -enriched product compared with the leukapheresis product and a 2.7-log reduction in the dose of CD38 ++ cells received at transplant.…”

“…38 Flow cytometric methods provided a simple, fast and reliable means to assess the effect of CD34 + selection on the tumour contamination of stem cell products enabling detection of as few as 1/1000-1/10 000 tumour cells. 13,41 Although molecular techniques based on polymerase chain reaction are more sensitive allowing detection of as few as 1/1000-1/10 000 tumour cells quantitative analysis is complex and labour intensive. 43 It also remains to be determined if the added sensitivity of molecular techniques is of clinical significance.…”

“…We have therefore set 0.05% as the lower level of sensitivity for the measurement of CD38 ++ cells, which is similar to the range of reported sensitivities of 0.01% and 0.1%. 13,40 Accordingly we have recorded values of 0.05% for all levels of CD38 ++ cells between 0% and 0.05% with the result that the calculated depletion of CD38 ++ cells is underestimated when the level of CD38 ++ cells is below 0.05% in the CD34 + -selected product. We have also excluded from our analysis results where less than 20 positive events were detected.…”

“…Light chain restriction studies by other groups have also validated high CD38 expression as a means of identifying plasma cells 40,41 that enables detection of as few as one tumour cell per 10 3 -10 4 total cells. 13,40 To validate the use of CD38 ++ to quantitate plasma cells we enumerated plasma cells in bone marrow smears from 20 patients and compared these estimates in a double-blind manner with the numbers of CD38 ++ cells estimated by flow cytometry in the corresponding marrow aspirate. There was significant linear correlation between plasma cell levels and the levels of CD38 ++ cells (r 2 = 0.82, P Ͻ 0.0001) (Figure 4a).…”

“…In MM there is also evidence that a prolonged high-dose treatment can reduce tumour burden and exert an in vivo purging effect on PBSC collections. 4,13,17 PBSC collections harvested at the end of a chemotherapy sequence contain significantly fewer plasma cells than those harvested upfront after a single high-dose drug administration.…”